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ALOX15-Inhibitory Peptides Derived from Coffee Bean Protein Hydrolysates Confer Neuroprotection against Lipid
Xiao-Min Lin1,2, Ya-Jing Han3, Wei-Xi Li3
1Department of Neurology, The First Affiliated Hospital of Jinan University/State Key Laboratory of Bioactive Molecules and Druggability Assessment, College of Pharmacy/Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs/Guangdong Engineering Research Center of Traditional Chinese Medicine & Disease Susceptibility/Guangdong Engineering Research Center of Traditional Chinese Medicine & Health Products/International Cooperative Laboratory of TCM Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE)/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research/The Affiliated Guangdong Second Provincial General Hospital, Jinan University, Guangzhou510632, China.
Abstract:
Coffee beans are widely consumed worldwide and are known for their central nervous system-stimulating effects, mainly attributed to caffeine and other small molecules. However, the neuroprotective potential of coffee bean-derived peptides remains largely unexplored. In this study, coffee bean protein hydrolysates (CBPH) exhibited protective effects against RSL3- and 6-OHDA-induced neuronal injury. Virtual screening and molecular docking targeting 15-lipoxygenase (ALOX15), a key enzyme involved in oxidative neuronal damage, identified eight candidate inhibitory peptides. Among them, FAR and FPSFRE showed significant ALOX15 inhibitory activity, reducing enzyme activity by 51.73 ± 21.54% and 91.61 ± 2.43%, respectively (p < 0.05). Consistently, both peptides significantly improved neuronal viability and attenuated oxidative stress-induced injury. Their direct interactions with ALOX15 were further confirmed by cellular thermal shift assay and molecular dynamics simulations. Moreover, FAR and FPSFRE ameliorated locomotor deficits in a 6-OHDA-induced zebrafish model, highlighting their potential as natural neuroprotective agents and functional food ingredients.
